The present invention relates to methods and apparatus for corneal collagen crosslinking (“CCXL”).
The vision of a human or other mammalian subject can be modified by crosslinking the collagen within the cornea of the eye. A photoactivated crosslinking facilitator such as riboflavin is applied to the cornea. Light at a wavelength selected to activate the crosslinking facilitator is applied. Where the crosslinking facilitator is riboflavin, the light typically is ultraviolet or blue light. The activated facilitator causes crosslinking of the collagen within the cornea. The crosslinking changes the mechanical properties of the cornea. For example, the crosslinking stiffens the cornea. These changes can result in stabilization of pathological conditions, such as keratoconus, or in alterations to the shape of the cornea. This technique can be used to correct defects in vision such as myopia, hyperopia, or astigmatism. For myopia (nearsightedness), the center of the cornea is stiffened; for hyperopia (farsightedness), an annulus around the periphery of the cornea is stiffened. For more complicated corrections such as astigmatism, custom patterns are used.
In some applications, the light is applied as a beam directed into the eye from a device remote from the eye. In other applications, the light is applied by a device which rests on the eye. As disclosed in U.S. Patent Application Publication No. 2014/0379054 (“the '054 Publication”) and U.S. Provisional Patent Application No. 61/839,016 (“the '016 Provisional”), the disclosures of which are hereby incorporated by reference herein, light can be applied to the eye through a structure having a form, size, and shape resembling that of a contact lens such as a scleral contact lens. The structure may incorporate an optically dispersive element. Light may be directed into the dispersive element and dispersed so that the dispersed light passes into the eye from the dispersive element. This arrangement has numerous advantages. For example, the patient may be able to close his or her eye during the treatment, so that the structure is disposed between the eyelid and the eye.
CCXL changes the mechanical properties of the cornea by creating chemical bonds between the protein layers in the corneal stroma. These bonds (crosslinks) increase the stiffness of the cornea in the region crosslinked. This increased stiffness changes the balance between the cornea tension and the intraocular pressure. Through mechanisms not completely understand in the field, within a few days to weeks of CCXL therapy, physiologic processes reshape the cornea. The amount of reshaping, and thus the degree of curvature correction, is determined by a number of treatment parameters, including the amount and rate of energy delivery, the treatment time and the aperture of the treated area on the cornea. The amount of reshaping also may be influenced by factors such as the oxygen saturation of the cornea during irradiation; the amount of crosslinking facilitator present in the cornea during irradiation and physiological differences between patients.
As with any therapeutic energy delivery modality, it is desirable to control the irradiation of the eye so as to deliver a dose of radiation which will yield the desired procedural outcome, such as a desired degree of reshaping. Because numerous factors control the relationship between the light energy applied to the cornea during irradiation and the amount of reshaping achieved, it is difficult to achieve a precise degree of reshaping by selecting a dose of energy in advance, based on a priori knowledge of a relationship between dose and reshaping, and then simply applying the selected dose.
The reshaping of the cornea after CCXL takes place over a few days to weeks after the procedure. Thus, the real time monitoring of corneal shape during irradiation cannot be used as a measurement during the procedure to control the dose of UV delivered.
It has been proposed to use Brillouin microscopy to monitor properties of the cornea in conjunction with corneal crosslinking. However, application of this approach in a clinical setting suffers from significant practical difficulties.
Accordingly, further improvement would be desirable.